PROJECT SUMMARY/ABSTRACT Although African Americans smoke at similar or lower rates than non-Hispanic whites, their rates of lung cancer incidence and mortality are significantly higher. Cigarette smoking contributes to approximately 80-90% of lung cancer deaths; however, it does not fully elucidate racial disparities in lung cancer development. Understanding mechanisms that contribute to racial disparities in lung cancer is a public health priority. Chronic inflammation is a well-known pathway that directly links cigarette use to lung cancer carcinogenesis, and smokers have an elevated level of C-reactive protein (CRP), a biomarker for systemic inflammation. Although smoking cessation leads to a reduction in CRP over time, studies have shown that CRP does not fully return to levels similar to never smokers. Thus, increased levels of CRP are associated with elevated risk of lung cancer in former smokers. Several studies have shown that African Americans in the general population have higher levels of CRP than non-Hispanic whites. However, no studies have documented race differences in long- term change in CRP levels among those who have quit smoking. Research is needed to understand differences in the mechanisms that predict how CRP levels change and eventually increase disease risk. Although African Americans have similar smoking rates than non-Hispanic whites, they experience disproportionate rates of obesity and post-cessation weight gain, or weight gain attributable to quitting smoking. This weight gain may compound inflammation-related disease risk in former smokers, underlying disparities seen in lung cancer development. The objective of our proposed study is to examine changes in obesity and inflammation in African American and non-Hispanic white ex-smokers. We aim to: a) characterize race differences in inflammation over time, b) examine race differences in the effect of obesity on inflammation change, and c) explore associations of race, obesity, and inflammation with lung cancer incidence. Data will be drawn from the Health and Retirement Study, a longitudinal panel study on middle-aged to older adults. Using random effects multilevel modeling, we will compare different types of obesity (i.e., general vs. abdominal) to determine whether there are unique effects on inflammation between races. We will use propensity scores to isolate effects of race. These advanced statistical techniques will strengthen causal inference and control for confounding of socio-demographic and behavioral factors. By isolating the obesity-inflammation effect in ex- smokers, we will be able to determine bio-behavioral mechanisms that may contribute to racial disparities in cancer risk, and ultimately incidence, taking into account lasting effects of smoking. Our results will help to elucidate the currently unknown mechanisms of lung cancer disparities and inform interventions and screening guidelines to target racial/ethnic minority groups at high-risk for lung cancer.